3-{5-[4-(Cyclopentyloxy)-2-hydroxybenzoyl]-2-[3-hydroxy-1,2-benzisoxazol-6-yl)methoxy]phenyl}propionic acid (hereinafter called as “T-5224”) has excellent anti-arthritis action and has an osteoclastic suppressing action by arthritic activity, and have been developed as an anti-rheumatic agent (patent document 1).
In patent document 1, a manufacturing process by the crystallization of T-5224 from mixed solvents of chloroform and methanol is described.
However, the crystal of T-5224 (hereinafter called as “type I crystal”) produced by this manufacturing process has following defects, (1) its specific volume is large, (2) it is easy to be charged with electricity, (3) it is not easy to be handled, (4) in the crystal, it contains chloroform and methanol which are the solvents (class 2), the amount of residue of which in a medicine should be regulated, and so forth.
Further, it is hardly to say that this manufacturing process is an industrially profitable manufacturing process because (5) waste liquid containing chloroform occurs in large quantities and environmental loads are large.
Therefore, the type I crystal cannot be satisfied as an active pharmaceutical ingredient.    [Patent document 1] international publication No. WO03/042,150 pamphlet